rs7623685

Variant names:

• chr3-124475302-A-C
• rs7623685
• NM_001388419.1:c.4101+570A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-124475302-A-C
• chr3-124475302-A-G
• chr3-124475302-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.4101+570A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,072 control chromosomes in the GnomAD database, including 13,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13636 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 5 publications found

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.4101+570A>C		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.4095+570A>C		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.4095+570A>C		intron	N/A	NP_001309917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.4101+570A>C		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.4095+570A>C		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.4068+570A>C		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62845 AN: 151952 Hom.: 13629 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62862 AN: 152072 Hom.: 13636 Cov.: 32 AF XY: 0.407 AC XY: 30264 AN XY: 74324

African (AFR) AF: 0.326 AC: 13509 AN: 41472

American (AMR) AF: 0.369 AC: 5631 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.173 AC: 894 AN: 5178

South Asian (SAS) AF: 0.452 AC: 2179 AN: 4826

European-Finnish (FIN) AF: 0.389 AC: 4111 AN: 10562

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32773 AN: 67972

Other (OTH) AF: 0.441 AC: 931 AN: 2112

Alfa AF: 0.461 Hom.: 71284

Bravo AF: 0.408

Asia WGS AF: 0.314 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7623685; hg19: chr3-124194149; COSMIC: COSV53757949;